β-lactam antibiotics have long been a reliable course of treatment for bacterial infections. However, with recent increases in resistance and rising populations of immunocompromised patients new β-lactams have been synthesized and tested. The Turos laboratory has recently discovered novel β-lactams that have a mode of action distinct from penicillin and other β-lactam antibiotics as cell lysis is not observed. In the current investigations, these compounds are shown to also have antifungal properties. The rising incidence and prevalence of invasive fungal infections has become an increasing concern. The most common fungal pathogens involved in these infections are species in the genus Candida. In this study antifungal activity is observed for a wide range of N-methylthio β-lactams against C. albicans, C. tropicalis, C. keyfr, C. glabrata, C. lusitinae, C. utilis, and C. parapsilosis. The structure-activity relationship based on studies of β−lactam derivatives leaving different substituents at various positions on the lactam ring are investigated, and the minimum inhibitory concentration values determined using standard methods. In studies towards understanding the mode of action, the products of the interaction between the drug and fungal cells in a suspension were investigated using nuclear magnetic resonance spectroscopy and transmission electron microscopy. The mode of action of these new lactams seems to be similar to that observed in bacteria, involving transfer of the methylthio group to a cellular thiol.
| Identifer | oai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-4958 |
| Date | 12 May 2006 |
| Creators | Culbreath, Marci |
| Publisher | Scholar Commons |
| Source Sets | University of South Flordia |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Graduate Theses and Dissertations |
| Rights | default |
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